Kinetic and Stability Study of an Investigative Antirhinovirus Compound

Abstract

A hydrolytic acid and base catalyzed ring opening reaction has been demonstrated for a 1,2,4-oxadiazole antiviral compound (WIN 63843) resulting mainly in an amidoxime product. Decomposition products and related impurities were detected using a gradient HPLC method. The hydrolysis reaction was first-order for 35% ethanol/buffer solutions in a 50°C chamber or a light cabinet (1000 ft-candles), the greatest stability being between pH 4 and 6. Furthermore, increasing ethanol concentrations resulted in a great decrease in reaction rates. Therefore, for oral or aerosol solution formulations, light protection, pH control between 4 and 6 and the highest permissible ethanol concentrations would be advantageous. This study has shown that the highly electronegative trifluoromethyl group at the 5 position increases the lability of a 1,2,3-oxdiazole compound.     

Oral Dosage Development of a Human Rhinovirus and Non-Polio Enterovirus Inhibitor

WIN 63843, a Picornavirus replication inhibitor, is physically and chemically stable in the solid state, to light, elevated temperature, and humidity. This 3-ary15-trifluoromethyl disubstituted 1,2,4-oxadiazole compound has very low water solubility but is highly soluble in ethanol and in safflower seed and corn oils. Solubility in the vegetable oils is doubled by the synergistic effect of ethanol at the 16% alcohol concentration. Vegetuble oil solutions of WIN 63843 are thermally stable but react slowly in the presence of light resulting in an amidoxime compound (WIN 65489) formed by opening of the 1,2,4-oxadiazole ring. This reaction does not occur in oil solutions containing small concentrations of ethanol. Of biophannaceutical interest, the addition of ethanol or PEG-400 solutions of WIN 63843 to human gastric fluid resulted in oily droplet formation whereas crystals form upon addition of these solutions to water. Also, the compound is greater than 8,000 times more soluble in human gastric fluid.     

Oral Dosage Development of a Human Rhinovirus and Non-Polio Enterovirus Inhibitor

Abstract

WIN 63843, a Picornavirus replication inhibitor, is physically and chemically stable in the solid state, to light, elevated temperature, and humidity. This 3-ary15-trifluoromethyl disubstituted 1,2,4-oxadiazole compound has very low water solubility but is highly soluble in ethanol and in safflower seed and corn oils. Solubility in the vegetable oils is doubled by the synergistic effect of ethanol at the 16% alcohol concentration. Vegetuble oil solutions of WIN 63843 are thermally stable but react slowly in the presence of light resulting in an amidoxime compound (WIN 65489) formed by opening of the 1,2,4-oxadiazole ring. This reaction does not occur in oil solutions containing small concentrations of ethanol. Of biophannaceutical interest, the addition of ethanol or PEG-400 solutions of WIN 63843 to human gastric fluid resulted in oily droplet formation whereas crystals form upon addition of these solutions to water. Also, the compound is greater than 8,000 times more soluble in human gastric fluid.     

N-中氮茚甲酰脲衍生物的合成及其作为pH值探针的研究

设计、合成了N-中氮茚甲酰脲衍生物4;紫外和荧光光谱研究表明,其在乙醇中具有较明显的紫外吸收峰和较强的荧光,pH值=10.02～12.48时荧光较强,且荧光强度与pH值有较好的线性关系.因此,该化合物有望作为10.02～12.48范围内的pH值探针.     

A novel polymerizable imidazole derivative for blue light-emitting material

A novel imidazole derivative, 2-(4-(2,5-dibutoxy-4-vinylstyryl)phenyl)-4,5-diphenyl-1H-imidazole) (VPDPI), as optoelectronic material was designed and synthesized by heck coupling reaction. The structure, thermal analysis and photoluminescence (PL) properties were investigated. The results indicate that the organic compound has good PL property. The emission peak of VPDPI is in the blue regions (465 nm), and the luminescence quantum yield is 0.61 in ethanol, which show that the compound emits blue light and is a desirable blue-emitting photoluminescence material. Also the organic compound shows better thermal stability due to the molecular structure introduced by imidazole heterocyle. The compound can be polymerized for the design of novel and efficient organic optoelectronic materials.     

NaLuF4:Yb,Tm up-conversion materials: Investigation of UV emission intensity by experimental design

NaLuF₄ doped Yb/Tm upconversion phosphor was synthesized by a facile hydrothermal method, using EDTA as a chelating agent. The influence of synthesis parameters was investigated on UV emission intensity through face-centered central composite design (CCD). Four parameters including F:RE ratio, pH value, reaction time and ethanol percent were considered as independent variables. It was found that pH value and F:RE ratio have the highest effect on emission intensity and the ethanol percent and the reaction time have mild and low influence on it. Furthermore, at pH 4, nano spherical particles with cubic phase were formed and change of other parameters had low influence on phase transformation. However, the hexagonal micro prisms with the hexagonal phase were predominant at pH?≥?6. The role of EDTA was indicated on phase transformation and aggregation of particles at the various value of pH. It was shown that the crystal phase, the surface smoothness and the particle size are influential factors on UV emission intensity.     

A kinetic model for the degradation of benzothiazole by Fe3+-photo-assisted Fenton process in a completely mixed batch reactor

The degradation of benzothiazole in aqueous solution by a photo-assisted Fenton reaction has been studied in a batch reactor in the pH range 2.0–3.2 and for H₂O₂ and Fe(III) concentrations respectively between 1.0×10⁻³–1.5×10⁻¹ and 1.0×10⁻⁶–4.0×10⁻⁶ M.

A kinetic model has been developed to predict the decay of benzothiazole at varying reaction conditions. The use of kinetic constants from the literature in the model allows to simulate the system behavior by taking into account the influence of pH, hydrogen peroxide, Fe(III) and sulfate concentrations and the ionic strength.     

水热合成单斜晶系BiVO4可见光催化剂及其性能

采用水热法合成了纯单斜晶系的可见光催化剂BiVO4,考察了水热温度、水热时间和体系的pH值对BiVO4结构和光催化性能的影响。利用XRD、SEM、BET和UV-VIS对样品进行了表征,结果表明:获得的BiVO4具有中空棒状结构,升高水热温度、提高反应溶液的pH值、延长水热时间有利于单斜晶系BiVO4的生成。确定了BiVO4的最优合成条件为:水热温度140℃,水热时间6h,反应体系pH=9。选择亚甲基蓝溶液作为光催化降解物质,研究BiVO4的可见光催化性能和催化机理。结果表明,最优条件下制备的BiVO4具有较好的可见光催化性能;同时,增加降解体系的pH值提高了催化剂对亚甲基蓝的吸附能力和活化电子的利用效率,有利于提高BiVO4的光催化性能。     

Kinetic study on photocatalytic degradation of C.I. Acid Yellow 23 by ZnO photocatalyst

The potential of a common semiconductor, ZnO, has been explored as an effective catalyst for the photodegradation of C.I. Acid Yellow 23 (AY23). The effects of process parameters such as, catalyst loading, initial dye concentration, light intensity, and pH on the extent of photodegradation have been investigated. Substantial reduction of COD, besides removal of color, was also achieved. A rate equation for the degradation based on Langmuir-Hinshelwood (L-H) model has been proposed. The results show that the adsorption constant (K(ads)) and rate constant (k(L-H)) in L-H model are dependent to the light intensity, and increase with increasing the light intensity. With inserting the light intensity parameter to L-H equation, this model can be used for predicting the removal rate at different light intensities and initial concentrations of AY23. A comparison between experimental and calculated apparent reaction rate constants shows that the results obtained from the L-H modified model are in good agreement with experimental data.     

Preformulation Development of a Human Leukocyte Elastase Inhibitor for Oral Dosage

Abstract

WIN 64733 solubility and partition coefficients were determined with a precise and accurate HPLC method. Solubility decreased with increasing pH (140 mg/mL at pH 2.0, 86 mg/mL at pH 3.8, and 48 mg/mL at pH 5.2) but equilibrated within 30 hours. In purified water the maximum concentration was 102 mg/mL with pH 3.6. The maximum solubility in hydroxypropyl-beta-cyclodextrin (HP-β-CD) is only 43 mg/mL. However, unlike the water solution, the cyclodextrin preparation did not precipitate when added to 0.1 N HCl or 0.9% NaCl. The precipitated chloride salt of WIN 64733 is amorphous. Excess compound that was wetted, but not dissolved, formed liquid crystals.

In human gastric fluid (HGF), WIN 64733 did not decompose in the solid or liquid state for 2 hours, or precipitate from solution despite NaCl and HCl in the HGF. WIN 64733 solid is stable to heat (50°C), light (1000 ft-candles), humidity (75% RH), and heat plus humidity for 6 weeks. Solutions of WIN 64733 are unstable, with first-order decomposition rates that are light independent at pH's 2.0 to 6.6. Decomposition was more rapid at higher pH's and increased temperature. This occurred by hydrolysis of the ester linkage forming an N-hydroxymethyl fragment that subsequently decomposed to saccharin and formaldehyde, verified by the Hantzsch reaction.

Since solubility is high in water and HGF, dissolution in the gastric environment would favor absorption of an oral dose.     

Prussian-blue-modified iron oxide magnetic nanoparticles as effective peroxidase-like catalysts to degrade methylene blue with H2O2

Prussian-blue (PB)-modified γ-Fe(2)O(3) magnetic nanoparticles (PBMNPs) were successfully synthesized based on electric interactions between negatively charged [Fe(CN)(6)](4-) and positively charged γ-Fe(2)O(3) nanoparticles. The in situ PB coating was generated by the coordinating reaction between the adsorbed [Fe(CN)(6)](4-) and the ferric ions on the surface of γ-Fe(2)O(3) NPs. The as-prepared PBMNPs were characterized by FT-IR, XRD, TEM, and used to remove organic pollutants from aqueous solution, namely, using methylene blue (MB) as model compound. The experimental results showed that the target compound could be removed efficiently from solution over a wide pH range from 3 to 10 in the presence of PBMNPs as peroxidase-like catalyst and H(2)O(2) as oxidant. Under optimal conditions, MB could be removed completely after 120 min of reaction at 298 K; the chemical oxygen demand (COD) removal efficiency and the total organic carbon (TOC) abatement efficiency were 53.6% and 35%, respectively. Furthermore, the PBMNPs catalysts showed high magnetization, temperature tolerance, long-term storage and operational stability, and they could be readily separated from solution by applying an external magnetic field. Finally, a possible reaction mechanism for MB degradation was also discussed.     

Kinetics of 2,6-dimethylaniline degradation by electro-Fenton process

A new approach for promoting ferric reduction efficiency using a different electrochemical cell and the photoelectro-Fenton process has been developed to degrade organic toxic contaminants. The use of UVA light and electric current as electron donors can efficiently initiate the Fenton reaction. 2,6-Dimethylaniline (2,6-DMA) was the target compound in this study. Effects of initial pH (pH(i)), Fe(2+) loading, H(2)O(2) concentration and current density were determined to test and to validate a kinetic model for the oxidation of organic compound by the electro-Fenton process. Kinetic results show evidence of pseudo-first-order degradation. When reaction pH was higher than 2, amorphous Fe(OH)(3(s)) was generated. Increasing ferrous ion concentration from 1.0 to 1.5 mM increased the hydroxyl radicals and then promote the degradation efficiency of 2,6-DMA. The optimal H(2)O(2) concentration for 2,6-DMA degradation in this study was 25 mM. The degradation of 2,6-DMA was increased with the increase of current density from 3.5 to 10.6 A/m(2). Oxalic acid was the major detected intermediate of 2,6-DMA degradation. The final TOC removal efficiencies were 10%, 15%, 60% and 84% using the electrolysis, Fenton, electro-Fenton and photoelectro-Fenton processes, respectively.     

One-step functionalization of graphene via Diels--Alder reaction for improvement of dispersibility

Good dispersibility of graphene in a medium or matrix is a critical issue in practical applications. In this work, graphene was functionalized using N-(4-hydroxyl phenyl) maleimide (4-HPM) via the Diels–Alder (DA) reaction by a one-step catalyst-free approach. The optimal reaction condition was found to be 90 °C for 12 h using dimethylformamide (DMF) as the solvent. FTIR, Raman spectroscopy, XPS and EDS proved that 4-HPM moieties were successfully grafted onto the surface of graphene. UV-vis and TGA confirmed that the grafting amount of 4-HPM was 3.75%–3.97% based on the mass of graphene. Functionalized graphene showed excellent dispersion stability when dispersed in common solvents such as ethanol, DMF, water, tetrahydrofuran and p-xylene. Meanwhile, functionalized graphene also exhibited pH sensitivity in aqueous due to the phenolic hydroxyls from the 4-HPM moieties. As a result of good dispersion stability and pH sensitivity, compared with graphene, functionalized graphene had better adsorption capacity for methylene blue (MB) from aqueous solution.     

Preparation of dendrimer SAM on Au substrate and adsorption/desorption of poly-L-glutamate on the SAM

A self-assembled monolayer (SAM) of a dendrimer has been fabricated by covalent bonding of amine-terminated dendrimers to 3-mercaptopropionic acid SAM on an Au substrate, where an amide bond was formed between the amine and the carboxylic acid using amide-coupling reagents. Each reaction step was inspected by transmission surface-enhanced infrared absorption spectroscopy. Reaction was affected by solvents of the coupling reagents and concentrations of the coupling reagents and dendrimers. The pH-dependent adsorption/desorption behavior of sodium poly-L-glutamate (PGA) has been examined on the dendrimer SAM prepared. The adsorbed amount was abundant at acid pH below the pK(a) of carboxylate, while desorption from PGA-adsorbed dendrimer SAM prepared at acid pH proceeded as the pH was raised. The reaction was reversible and reproducible within 30 min under controlled pH, although the carboxylic acid species adsorbed at pH 4.2 was deprotonated to a carboxylate species after more than 30 min of desorption at pH 9.4.     

固体超强酸SO_4~(2-)/TiO_2-Fe_2O_3光催化降解含酚废水

采用固体超强酸SO42-/TiO2-Fe2O3为光催化剂,苯酚的光催化降解为模型反应,考察了pH值、苯酚初始浓度、催化剂投加量、光照距离、光照时间、助催化剂H2O2对光催化降解过程的影响。结果表明,苯酚初始浓度为50mg/L,催化剂投加量5g/L,光照距离11cm,光照时间为150min,降解率达61.29%,添加助催化剂H2O2后,反应60min,苯酚降解率达到85.12%。     

PbS插层K4Nb6O17复合物的制备及其光催化制氢活性

采用固相法合成层状半导体K4Nb6O17,通过层间离子交换反应、胺插入反应以及硫化反应制备了纳米PbS插层的K4Nb6O17复合光催化剂(记作K4Nb6O17/PbS).利用X射线衍射(XRD),场发射扫描电镜(SEM),X射线荧光光谱仪(XRF),紫外可见漫反射(UV-Vis)和分子荧光光谱(PL)等技术对其进行表征.考察了催化剂在Na2SO3和Na2S为牺牲剂的光催化制氢活性.结果表明,PbS的插层拓展了K4Nb6O17对可见光的响应,催化制氢活性也有明显提高.在紫外光和可见光下3 h产氢量分别达到123.94和0.66 mmol/(g cat).最后讨论了插层复合催化剂光生电荷转移的机理.     

Surface Preparation of Aluminum Nitride for Metallization

Currently, the surface preparation of aluminum nitride (AlN) substrates prior to metallization includes an aqueous cleaning step. Surface reactions that occur in this step cause performance and reliability issues with AlN substrates to be used in microelectronic packaging. There is a lack of published data on the reactivity of AlN substrates with common solvents. This study investigated the effects of different solvents on the surface corrosion of AlN substrates. The variables studied were pH, aqueous vs. organic solutions, prior surface condition, and time (up to 3.6 Ms or 42 days). The solvents tested were hydrochloric acid (HCl) with pH values ranging from 2 to 5, sulfuric acid (H₂SO₄) with pH values ranging from 2 to 5, sodium hydroxide (NaOH) with pH values ranging from 8 to 12, 1 M citric acid, oleic acid, Micro-90, methanol, ethanol, isopropanol, acetone, and deionized water. Three types of surface reaction behavior were observed in this study. The substrates either showed no reaction (HCl pH = 2, methanol, ethanol, isopropanol, acetone, citric acid, and oleic acid), slight corrosion without spalling (Micro-90, HCl pH = 3, H₂SO₄pH = 3), or they were severely corroded and spalled (HCl pH = 5, H₂SO₄pH = 5, all NaOH solutions, and deionized water).     

原料奶中尿的掺假定性检测方法

研究了原料乳中尿的检测方法,尿中含有肌酐,复合苦味酸肌酐就是在pH值为12的条件下,肌酐与苦味酸反应而成的。通过颜色的变化判断鲜乳中是否有尿的存在。结果表明,该方法用于检测原料乳中尿含量在4%以上含量具有明显的颜色变化,同时方法操作简单,结果判定较直观。适用于乳品企业进行尿定性的检测。     

一种笼形超分子主体化合物Cryptophane E的合成与表征

以香草醛为原料,在乙醇介质中与1,3-二溴丙烷反应生成1,3-二(4-甲酰-2-甲氧基苯氧基)丙烷,然后在甲醇介质中进行硼氢化还原,最后在甲酸介质中聚合,合成笼形超分子主体化合物Cryptophane E.采用核磁共振谱(1H NMR、13C NMR)、质谱(MS)、紫外光谱(UV)荧光光谱、红外光谱、元素分析等测试技术对Cryptophane E进行表征,重点考察反应温度、时间及原料配比等因素对合成产率的影响,获得最佳反应条件,并深入探讨了合成机理.     

助剂对紫外荧光喷墨油墨发光性能的影响

为了获得衰减不明显的高荧光强度的紫外荧光喷墨油墨,选用乙醇和三乙醇胺分别作为干燥剂和pH 值调节剂,配制油墨样品,探讨了乙醇和三乙醇胺含量对荧光强度的影响;选用不同种类及含量的紫外吸收剂,分别制备油墨样品,探讨了紫外吸收剂种类和含量对荧光强度、荧光衰减的影响。结果表明,随着乙醇含量的增加,三乙醇胺含量的降低,荧光强度显著增强;紫外吸收剂UV-7292 对荧光强度影响较小,且能改善油墨的耐光性能。在满足其它性能的前提下,当乙醇、三乙醇胺和紫外吸收剂UV-7292 的质量分数分别为15%,0. 6%和0. 5%时,紫外荧光喷墨油墨发光性能最佳。